Sabine Strehl

Publications (85) View all

• Source

  Available from: Andishe Attarbaschi

  Article: Treatment outcome of CRLF2 -rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP-BFM and UK NCRI-CCLG study groups.

  Andishe Attarbaschi, Maria Morak, Gunnar Cario, Giovanni Cazzaniga, Hannah M Ensor, Truus te Kronnie, Jutta Bradtke, Georg Mann, Elena Vendramini, Chiara Palmi, [......], Valentino Conter, Christopher D Mitchell, Sabine Strehl, Martin Zimmermann, Ulrike Pötschger, Christine J Harrison, Martin Stanulla, Renate Panzer-Grümayer, Oskar A Haas, Anthony V Moorman
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  ABSTRACT: The prognostic relevance of CRLF2 -rearrangements in childhood acute B-cell precursor lymphoblastic leukaemia (ALL), was assessed by a comparative analysis of 114 non-Down-syndrome patients (99 P2RY8-CRLF2+ , 15 IGH@-CRLF2+ ), 76 from the AIEOP-BFM ALL 2000 and 38 from the MRC ALL97 trials. The 6-year cumulative relapse incidence of P2RY8-CRLF2+ patients treated on the two trials was not statistically different: 0·37 ± 0·06 vs. 0·25 ± 0·08 (P = 0·194). In contrast, 0/9 IGH@-CRLF2+ AIEOP-BFM, but 5/6 ALL97 patients relapsed. Conclusively, P2RY8-CRLF2+ patients had an intermediate protocol-independent outcome while the different prognosis of IGH@-CRLF2+ patients could be related to the different structures of the applied treatment protocols.
  British Journal of Haematology 07/2012; 158(6):772-7. · 4.94 Impact Factor
• Article: PAX5-AUTS2: a recurrent fusion gene in childhood B-cell precursor acute lymphoblastic leukemia.

  Dagmar Denk, Karin Nebral, Jutta Bradtke, Gertrud Pass, Anja Möricke, Andishe Attarbaschi, Sabine Strehl
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  ABSTRACT: PAX5 rearrangements resulting in the expression of fusion transcripts account for 2-3% of childhood B-cell precursor acute lymphoblastic leukemia. Most PAX5 fusions are rare and many of them have only been described in a couple of, or even only in single, cases. We have identified the third case with a PAX5-AUTS2 fusion, which results from unbalanced t(7;9)(q11.2;p13.2) rearrangements. Our findings substantiate that PAX5-AUTS2 is a recurrent fusion gene in pediatric B-cell precursor acute lymphoblastic leukemia, and we summarize the clinical characteristics of such patients.
  Leukemia research 05/2012; 36(8):e178-81. · 2.36 Impact Factor
• Article: Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study.

  Eva A Coenen, Susana C Raimondi, Jochen Harbott, Martin Zimmermann, Todd A Alonzo, Anne Auvrignon, H Berna Beverloo, Myron Chang, Ursula Creutzig, Michael N Dworzak, [......], Jan Stary, Irina Stasevich, Sabine Strehl, Takashi Taga, Daisuke Tomizawa, David Webb, Zuzana Zemanova, Rob Pieters, C Michel Zwaan, Marry M van den Heuvel-Eibrink
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  ABSTRACT: We previously demonstrated that outcome of pediatric 11q23/MLL-rearranged AML depends on the translocation partner (TP). In this multicenter international study on 733 children with 11q23/MLL-rearranged AML, we further analyzed which additional cytogenetic aberrations (ACA) had prognostic significance. ACAs occurred in 344 (47%) of 733 and were associated with unfavorable outcome (5-year overall survival [OS] 47% vs 62%, P < .001). Trisomy 8, the most frequent specific ACA (n = 130/344, 38%), independently predicted favorable outcome within the ACAs group (OS 61% vs 39%, P = .003; Cox model for OS hazard ratio (HR) 0.54, P = .03), on the basis of reduced relapse rate (26% vs 49%, P < .001). Trisomy 19 (n = 37/344, 11%) independently predicted poor prognosis in ACAs cases, which was partly caused by refractory disease (remission rate 74% vs 89%, P = .04; OS 24% vs 50%, P < .001; HR 1.77, P = .01). Structural ACAs had independent adverse prognostic value for event-free survival (HR 1.36, P = .01). Complex karyotype, defined as ≥ 3 abnormalities, was present in 26% (n = 192/733) and showed worse outcome than those without complex karyotype (OS 45% vs 59%, P = .003) in univariate analysis only. In conclusion, like TP, specific ACAs have independent prognostic significance in pediatric 11q23/MLL-rearranged AML, and the mechanism underlying these prognostic differences should be studied.
  Blood 05/2011; 117(26):7102-11. · 9.90 Impact Factor
• Article: Expression of PAX5 splice variants: a phenomenon of stress-induced, illegitimate splicing?

  Karin Nebral, Daniela Krehan, Sabine Strehl
  British Journal of Haematology 04/2011; 155(2):277-80. · 4.94 Impact Factor
• Article: ETV6/RUNX1-positive relapses evolve from an ancestral clone and frequently acquire deletions of genes implicated in glucocorticoid signaling.

  Lilian Kuster, Reinhard Grausenburger, Gerhard Fuka, Ulrike Kaindl, Gerd Krapf, Andrea Inthal, Georg Mann, Maximilian Kauer, Johannes Rainer, Reinhard Kofler, Andrew Hall, Markus Metzler, Lüder Hinrich Meyer, Claus Meyer, Jochen Harbott, Rolf Marschalek, Sabine Strehl, Oskar A Haas, Renate Panzer-Grümayer
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  ABSTRACT: Approximately 25% of childhood acute lymphoblastic leukemias carry the ETV6/RUNX1 fusion gene. Despite their excellent initial treatment response, up to 20% of patients relapse. To gain insight into the relapse mechanisms, we analyzed single nucleotide polymorphism arrays for DNA copy number aberrations (CNAs) in 18 matched diagnosis and relapse leukemias. CNAs were more abundant at relapse than at diagnosis (mean 12.5 vs 7.5 per case; P=.01) with 5.3 shared on average. Their patterns revealed a direct clonal relationship with exclusively new aberrations at relapse in only 21.4%, whereas 78.6% shared a common ancestor and subsequently acquired distinct CNA. Moreover, we identified recurrent, mainly nonoverlapping deletions associated with glucocorticoid-mediated apoptosis targeting the Bcl2 modifying factor (BMF) (n=3), glucocorticoid receptor NR3C1 (n=4), and components of the mismatch repair pathways (n=3). Fluorescence in situ hybridization screening of additional 24 relapsed and 72 nonrelapsed ETV6/RUNX1-positive cases demonstrated that BMF deletions were significantly more common in relapse cases (16.6% vs 2.8%; P=.02). Unlike BMF deletions, which were always already present at diagnosis, NR3C1 and mismatch repair aberrations prevailed at relapse. They were all associated with leukemias, which poorly responded to treatment. These findings implicate glucocorticoid-associated drug resistance in ETV6/RUNX1-positive relapse pathogenesis and therefore might help to guide future therapies.
  Blood 01/2011; 117(9):2658-67. · 9.90 Impact Factor